Fig. 1.

Mathematical model of Ca²⁺/calmodulin-dependent protein kinase (CaMKII) signaling in human atrial myocyte. A: the structure of voltage-gated Na⁺ channel α-subunit Na_v1.5. Ser⁵⁷¹ in the DI-DII loop is critically important for CaMKII-dependent regulation of late Na⁺ current (I_Na,L) (16). B: schematic of key plasma membrane ion currents and sarcoplasmic reticulum (SR) protein channels in the Grandi atrial cell model (18). I_Ca,L, L-type Ca²⁺ current; I_Na, fast Na⁺ current; I_Kur, ultrarapid delayed rectifier K⁺ current; I_Ks, slow delayed rectifier K⁺ current; I_Kr, rapid delayed rectifier K⁺ current; I_K1, inward rectifier K⁺ current; I_to, 4-aminopyridine-sensitive transient outward K⁺ current; J_SR,up, Ca²⁺ uptake into the SR; I_NCX, Na⁺/Ca²⁺ exchanger current; I_NaK, Na⁺-K⁺ pump ATPase; I_Cl,b, background Cl⁻ current; I_Na,b, background Na⁺ current; I_Ca,b, background Ca²⁺ current; I_CaCl, Ca²⁺-activated Cl⁻ current; I_pCa, sarcolemmal Ca²⁺ pump. CaMKII activation by Ca²⁺/calmodulin and downstream targeting of RyR2, I_up, I_Ca,L, and I_Na,L is included in this updated model.